title: Deletions of IKZF1 and SPRED1 are associated with poor prognosis in a population-based series of pediatric B-cell precursor acute lymphoblastic leukemia diagnosed between 1992 and 2011.
abstract: Despite the favorable prognosis of childhood acute lymphoblastic leukemia (ALL), a substantial subset of patients relapses. As this occurs not only in the high risk but also in the standard/intermediate groups, the presently used risk stratification is suboptimal. The underlying mechanisms for treatment failure include the presence of genetic changes causing insensitivity to the therapy administered. To identify relapse-associated aberrations, we performed single-nucleotide polymorphism array analyses of 307 uniformly treated, consecutive pediatric ALL cases accrued during 1992-2011. Recurrent aberrations of 14 genes in patients who subsequently relapsed or had induction failure were detected. Of these, deletions/uniparental isodisomies of ADD3, ATP10A, EBF1, IKZF1, PAN3, RAG1, SPRED1 and TBL1XR1 were significantly more common in B-cell precursor ALL patients who relapsed compared with those remaining in complete remission. In univariate analyses, age (≥10 years), white blood cell counts (>100 × 10(9)/l), t(9;22)(q34;q11), MLL rearrangements, near-haploidy and deletions of ATP10A, IKZF1, SPRED1 and the pseudoautosomal 1 regions on Xp/Yp were significantly associated with decreased 10-year event-free survival, with IKZF1 abnormalities being an independent risk factor in multivariate analysis irrespective of the risk group. Older age and deletions of IKZF1 and SPRED1 were also associated with poor overall survival. Thus, analyses of these genes provide clinically important information.
authors.affiliation: Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Olsson
authors.affiliation: Department of Pediatrics, Skåne University Hospital, Lund, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Castor
authors.affiliation: Department of Pediatrics, Linköping University Hospital, Linköping, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Behrendtz
authors.affiliation: Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Biloglav
authors.affiliation: Department of Medical Bioscience, University of Umeå, Umeå, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Forestier
authors.affiliation: Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Paulsson
authors.affiliation: 1] Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden [2] Department of Clinical Genetics, University and Regional Laboratories Region Skåne, Lund, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Johansson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C497239:IKZF1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C504812:SPRED1 protein, human; D051740:Ikaros Transcription Factor